Glycoconjugates interact specifically with microbial lectins, e.g. viral envelope proteins, bacterial adhesins and toxins (20). The specificity is provided by saccharide sequences, e.g. the GM1 ganglioside recognized by cholera toxin (9, 10) Gal 1.fwdarw.4Gal by uropathogenic E. coli (14, 16), or GlcNAc 1.fwdarw.3Gal by Streptococcus pneumoniae (2). When membrane bound, the glycoconjugates act as receptors, and the interaction with e.g. bacteria results in the attachment thereof to the receptor-bearing cell (17). When secreted these oligosaccharide sequences have other functions. For example, the presence in external secretions of oligosaccharide sequences corresponding to the cell-bound receptors provides the basis for competitive inhibition of microbial binding (3). Since attachment to epithelial cells is an important event in the pathogenesis of many bacterial infections, inhibition of attachment by secreted oligosaccharides may protect against infection (EP-A1-0 126 043).
Human milk is a rich source of free oligosaccharides and glycoconjugates (12, 13). Human milk inhibits the attachment both of S. pneumoniae and H. influenzae to nasopharyngeal epithelial cells in vitro (3). Inhibitors for pneumococcal binding were identified in the free oligosaccharide fraction, as expected from its content of lacto and neolactotetraose with known receptor activity for pneumococci (3).
Additional components of a molecular weight of &gt;5000 daltons but not of immunoglobulin nature were also found to interact with both S. pneumoniae and H. influenzae (3). The present invention describes the identification of these non-immunoglobulin components in the high molecular weight fraction of human milk as caseins.